The gastric enterochromaffin-like (ECL) cell is the cell responsible for histamine release within the gastric fundic mucosa, deemed essential for activation of the H2 receptor on the parietal cell. It therefore plays a central role in regulation of acid secretion. It constitutes 1% of cell volume in fundic epithelium. It has been isolated and purified to 85% cell content from rat gastric mucosa, by a combination of elutriation, density gradient centrifugation and short term culture. Histamine release is stimulated by gastrin/CCK, carbachol and epinephrine and inhibited by somatostatin, H3 receptor agonist and CCK B antagonists. The mechanisms of stimulus secretion coupling in this cell are unknown. These will be investigated by image analysis of changes in intracellular calcium, chloride and pH, by cell attached and whole cell measurements and by defining the proteins involved in granule exocytosis by screening a cDNA library derived from the purified ECL-cell preparation. These data will allow a novel understanding of the peripheral regulation of gastric acid secretion as well as the exocytotic process in a non- excitable endocrine cell.